Weekly Dose: Digoxin, the heart medicine that may have given us Van Gogh’s Starry Night

Author

Disclosure statement

Andrew McLachlan is the Program Director for the NHMRC Centre for Resarch Excellence in Medicines and Ageing. He was an investigator on the PACE trial (ACTRN 12609000966291) which was an investigator-initiated trial evaluating paracetamol for acute low back pain funded by the NHMRC and GlaxoSmithKline and the PRECISE trial (ACTRN12613000530729) which is an investigator-initiated trial evaluating pregabalin for sciatica funded by NHMRC and in kind research support from Pfizer (providing medicines and placebo). He has received research funding support from GlaxoSmithKline for a postgraduate scholarship under his direct supervision and he has been an invited speaker at educational sessions and symposia directly sponsored by Bayer Australia and Gilead Sciences.

Digoxin is a drug used to treat heart failure and irregular heartbeats known as a “cardiac glycoside”. It is obtained from the leaves of the foxglove plant (Digitalis lanata) and is available in Australian as the brands Lanoxin and Sigmaxin.

How it works

Digoxin is used in people with heart failure because of its ability to increase the force of heart muscle (myocardial) contraction, which improves its pumping power. It also decreases oxygen consumption, which helps the heart do more with less oxygen.

Digoxin works by inhibiting the sodium pump within heart muscle cells. This increases sodium in the cells, which in turn increases calcium content, leading to increased force of heart contractions. Digoxin also has effects on electrical activity in the heart and is most widely used in people with abnormal heart rhythm (atrial fibrillation).

In the modern era, digoxin was considered, for many years, the mainstay of treatment for people with heart failure. However, this has changed over the last decade as it has been replaced as first-line treatment with other medicines which are generally safer to use and known to improve patient survival.

Evidence from clinical trials found treatment with digoxin did not reduce mortality in people with heart failure. The drug is now recommended as second-line treatment for people with severe heart failure who also have heart rhythm problems.

How it was developed

Digoxin was first isolated from the foxglove plant by Dr Sydney Smith at Burroughs Wellcome in Britain in 1930.

Even in these trials Withering identified that, while foxglove extract could help his patients, it was associated with severe side effects in some people, which he described as vomiting, purging, giddiness, confused vision and slow pulse.

How it makes you feel

Digoxin is known to have a narrow safety margin – the dose used for effective treatment is close to the dose that can cause adverse effects. At the correct dosage digoxin will reduce a patient’s heart palpitations and improve their symptoms of heart failure (which includes reducing shortness of breath).

If the dosage is too high, patients can experience delirium and depression, and it can adversely affect heart rhythm (arrhythmia), causing palpitations (or worse, death).

Digoxin is one of the few medicines in current use where we have a specific antidote for people who are experiencing digoxin toxicity. Called DigiFab (digoxin-specific antibody fragment), this can reduce the concentrations of the drug in the body.

Digoxin is not suitable for everyone, especially people with complicated types of heart rhythm problems because digoxin can make these problems worse. Careful dosing is particularly needed in older people (especially if they have poor kidney function) and young children with a heart condition. The common digoxin brand name for the lower dose (62.5 micrograms) is Lanoxin PG, where the “PG” refers to Paediatric and Geriatric.

Interactions and side effects

Digoxin interacts with a range of other medicines that people may be taking, including St John’s wort, which reduces the effectiveness of digoxin.

Cost and use

Digoxin is relatively inexpensive — costing patients around 20 cents a tablet on the Pharmaceutical Benefits Scheme — and less expensive if a person has a concession card.

Digoxin is a relatively common medicine for heart conditions. In the last 12 months, 350,000 prescriptions for digoxin were dispensed on the Pharmaceutical Benefits Scheme in Australia. However, its use is declining since medications with greater proven effectiveness and safety are preferred.

Among these diagnoses is the suspicion that he suffered from digitalis (foxglove) toxicity, which resulted in the frequent use of yellow halos in his paintings due to xanthopsia. This is very evident in paintings such as Starry Night
and The Night Café.

Others argue digitalis toxicity could not have caused Vincent’s yellow palette because sustaining that level of xanthopsia would have surely been lethal and Dr Gachet was unlikely to overdose Van Gogh because he practised homeopathy. But it does make for an interesting story, and an even better painting!